cellular phenotype

• abnormal airway basal cell differentiation
  • after polidocanol-induced acute injury, 8-wk old mutant mice display delayed regeneration of the tracheal epithelium with a transient hyperplasia of basal cells observed on days 4 and 6, but not on day 8, after injury
  (MGI Ref ID J:154705)

hematopoietic system phenotype

• decreased IgG level
  (MGI Ref ID J:103908)

• decreased immunoglobulin level
  • significantly reduced preimmune serum Ig levels
  (MGI Ref ID J:103908)

immune system phenotype

• decreased IgG level
  (MGI Ref ID J:103908)

• decreased immunoglobulin level
  • significantly reduced preimmune serum Ig levels
  (MGI Ref ID J:103908)

mammalian phenotype

• immune system phenotype
  • Normal - IgM levels of preimmune serum are little altered from control levels
  (MGI Ref ID J:103908)

respiratory system phenotype

• airway basal cell hyperplasia
  • at 1 year of age, the % of 1-2 layers of basal cells in the tracheal epithelium is reduced whereas the % of 3-4 layers of basal cells in increased by 3.8-fold relative to that in wild-type controls
  (MGI Ref ID J:154705)

• abnormal airway basal cell differentiation
  • after polidocanol-induced acute injury, 8-wk old mutant mice display delayed regeneration of the tracheal epithelium with a transient hyperplasia of basal cells observed on days 4 and 6, but not on day 8, after injury
  (MGI Ref ID J:154705)

nervous system phenotype

• abnormal nicotine-mediated receptor currents
  • hippocampal neurons from mutant mice do not exhibit rapidly desensitizing, methyllycaconitine-sensitive nicotinic currents
  (MGI Ref ID J:44288)

• abnormal brain morphology
  • Normal - however, autoradiography with [3H]nicotine revealed normal levels of high-affinity nicotine binding
  (MGI Ref ID J:44288)
  • homozygotes lack high-affinity [125I]alpha-bungarotoxin binding sites
  (MGI Ref ID J:44288)

reproductive system phenotype

• reduced fertility
  • homozygotes do not breed well
  (MGI Ref ID J:44288)

hematopoietic system phenotype

• increased lymphocyte cell number
  • increased lymphocytes in bone marrow
  (MGI Ref ID J:140280)

• decreased neutrophil cell number
  • fewer band neutrophils in bone marrow
  (MGI Ref ID J:140280)

• decreased erythroblast number
  • fewer erythroblasts and pro-normoblasts found in bone marrow
  (MGI Ref ID J:140280)

• abnormal myeloblast morphology/development
  • fewer myeloblasts and metamyeloblasts in bone marrow
  (MGI Ref ID J:140280)

immune system phenotype

• decreased neutrophil cell number
  • fewer band neutrophils in bone marrow
  (MGI Ref ID J:140280)

• increased lymphocyte cell number
  • increased lymphocytes in bone marrow
  (MGI Ref ID J:140280)

mammalian phenotype

• nervous system phenotype
  • Normal - homozygotes display normal growth, survival, gait, and anatomy and show no developmental abnormalities in the nervous system
  (MGI Ref ID J:44288)

immune system phenotype

• abnormal tumor necrosis factor level
  • following endotoxin administration, homozygotes show significantly higher levels of serum TNF levels as well as higher TNF production in the liver and spleen relative to wild-type
  (MGI Ref ID J:89610)
  • mutant macrophages are refractory to cholinergic agonists and generate TNF normally in the presence of nicotine or acetylcholine
  (MGI Ref ID J:89610)
  • electrical stimulation of the vagus nerve inhibits endotoxin-induced serum TNF levels in wild-type mice, but fails to reduce serum TNF levels in endotoxemic homozygotes
  (MGI Ref ID J:89610)

• abnormal interleukin level
  • endotoxemic homozygotes produce significantly higher levels of IL-1 and IL-6
  (MGI Ref ID J:89610)

mammalian phenotype

• behavior/neurological phenotype
  • Normal - homozygotes exhibit normal base-line learning and memory performance, and normal sensorimotor gating relative to wild-type
  (MGI Ref ID J:51149)
  • Normal - also, homozygotes are behaviorally similar to wild-type mice in a wide variety of behavioral tests
  (MGI Ref ID J:51149)
  • Normal - significant gender differences are noted in several tests; however, there is no evidence suggesting that these gender differences are genotype-specific
  (MGI Ref ID J:51149)

nervous system phenotype

• abnormal seizure response to pharmacological agent
  • neither cholinergic compensatory mechanisms nor alterations in binding levels or affinity for nicotinic ligands, such as epibatidine or nicotine, can account for the retained sensitivity to the convulsant effects of nicotine
  (MGI Ref ID J:74703)
  • homozygotes and wild-type mice display a similar dose-response curve for nicotine-elicited clonic-tonic seizures
  (MGI Ref ID J:74703)

behavior/neurological phenotype

• abnormal spatial learning
  • homozygotes locate the hidden platform in the Morris water task significantly faster than wild-type; however, this is a subtle difference and is not supported by the distance traveled data
  (MGI Ref ID J:51149)
  • also, homozygotes and wild-type mice show a comparable search behavior during the probe trials
  (MGI Ref ID J:51149)

• abnormal seizure response to pharmacological agent
  • homozygotes and wild-type mice display a similar dose-response curve for nicotine-elicited clonic-tonic seizures
  (MGI Ref ID J:74703)
  • neither cholinergic compensatory mechanisms nor alterations in binding levels or affinity for nicotinic ligands, such as epibatidine or nicotine, can account for the retained sensitivity to the convulsant effects of nicotine
  (MGI Ref ID J:74703)

• decreased anxiety-related response
  • however, this difference in altered anxiety-related behavioral response is not corroborated by the light<->dark exploration test
  (MGI Ref ID J:51149)
  • homozygotes spend a significantly greater proportion of their total distance traveled in the open field in the center of the arena relative to wild-type
  (MGI Ref ID J:51149)

homeostasis/metabolism phenotype

• abnormal tumor necrosis factor level
  • following endotoxin administration, homozygotes show significantly higher levels of serum TNF levels as well as higher TNF production in the liver and spleen relative to wild-type
  (MGI Ref ID J:89610)
  • mutant macrophages are refractory to cholinergic agonists and generate TNF normally in the presence of nicotine or acetylcholine
  (MGI Ref ID J:89610)
  • electrical stimulation of the vagus nerve inhibits endotoxin-induced serum TNF levels in wild-type mice, but fails to reduce serum TNF levels in endotoxemic homozygotes
  (MGI Ref ID J:89610)

• abnormal interleukin level
  • endotoxemic homozygotes produce significantly higher levels of IL-1 and IL-6
  (MGI Ref ID J:89610)

taste/olfaction phenotype

• impaired olfaction
  • mice exhibit deficits in detecting or discriminating chemically-related odors
  (MGI Ref ID J:166638)

taste/olfaction phenotype

• impaired olfaction
  • mice exhibit deficits in detecting or discriminating chemically-related odors
  (MGI Ref ID J:166638)

nervous system phenotype

• abnormal brain interneuron morphology
  • development of parvalbumin-positive GABAergic interneurons is disrupted in cortical cultures
  (MGI Ref ID J:214099)
  • development and maturation of cortical parvalbumin-positive basket cells is impaired in cortical cultures
  (MGI Ref ID J:214099)
  • NMDA receptor expression is reduced in cortical GABAergic interneurons of cortical cultures
  (MGI Ref ID J:214099)
  • GABAAalpha1 levels are reduced in parvalbumin-positive GABAergic interneurons in the prefrontal cortex
  (MGI Ref ID J:214099)
  • parvalbumin and GAD67 levels are reduced in the soma of parvalbumin-positive GABAergic interneurons
  (MGI Ref ID J:214099)

• decreased CNS synapse formation
  • marker analysis indicates that cortical GABAergic synapse formation is impaired in prefrontal cortex and in cortical cultures
  (MGI Ref ID J:214099)
  • formation of parvalbumin- and GAD65-positive perisomatic synapses is impaired in cortical cultures
  (MGI Ref ID J:214099)

• abnormal GABAergic neuron physiology
  • cortical GABAergic synaptic defects in the prefrontal cortex and in cortical cultures
  (MGI Ref ID J:214099)

• abnormal cerebral cortex morphology
  • cortical levels of GABAergic makers (parvalbumin, glutamic acid decarboxylase 65/67 (GAD65/67) and the alpha1 subunit of GABAA receptors) are decreased during late postnatal development and adulthood
  (MGI Ref ID J:214099)

• abnormal GABAergic neuron morphology
  • levels of markers of GABAergic maturation are reduced in the neocortex indicating that cortical parvalbumin GABAergic development is impaired
  (MGI Ref ID J:214099)

• abnormal GABA-mediated receptor currents
  • cultured cortical pyramidal neurons show a reduction in sIPSC frequency and current decay time, but not amplitude, indicating reduced GABAergic neurotransmission
  (MGI Ref ID J:214099)

• abnormal cerebral cortex pyramidal cell morphology
  • GABAAalpha1 levels are reduced in pyramidal neurons of the prefrontal cortex
  (MGI Ref ID J:214099)

behavior/neurological phenotype

• abnormal spatial working memory
  • in the delayed matching-to-place task of the Morris water maze, mutants take longer to find the hidden platform than controls, indicating a minor impairment in working/episodic memory
  (MGI Ref ID J:123663)
  • Normal - however, mice show normal latency to enter the central zone of the open field, normal elevated plus maze behavior, and no differences in swim speed or thigmotaxic behavior
  (MGI Ref ID J:123663)

reproductive system phenotype

• asthenozoospermia
  • many nonmotile sperm exhibit a quivering head and midpiece but no forward movement, confirming that cells are alive
  (MGI Ref ID J:115434)
  • Normal - however, no significant differences in sperm viability, senescence rate or spontaneous acrosome reaction rate are observed between mutant and wild-type sperm before and after capacitation
  (MGI Ref ID J:115434)
  • mutant sperm initially appear to swim normally but fail to maintain progressive forward motility
  (MGI Ref ID J:115434)
  • only few mutant sperm retain rapid swimming velocities and display hyperactivated swimming patterns following in vitro capacitation
  (MGI Ref ID J:115434)

• prolonged estrous cycle
  • the extent of asynchrony is variable within the mutant female population, but for a given animal, the average cycle length tends to remain stable at young mature ages (4-6 months) and middle ages (10-14 months)
  (MGI Ref ID J:92540)
  • female homozygotes show asynchronous, prolonged estrous cycles, with an average cycle length of 7.1 ¿ 0.68 days relative to wild-type and heterozygous females (4.3 ¿ 0.19 and 4.3 ¿ 0.10 days, respectively)
  (MGI Ref ID J:92540)
  • all female homozygotes eventually complete an estrous cycle, and may achieve pregnancy but with a smaller number of surviving pups
  (MGI Ref ID J:92540)

• reduced female fertility
  • the number of live births is significantly less from matings of female homozygotes with either heterozygous (4.5 ¿ 2.12) or homozygous (3.7 ¿ 0.53) mutant males in comparison to matings of heterozygous females and males (7.34 ¿ 0.04) and matings of heterozygous females and homozygous mutant males (7.1 ¿ 0.40)
  (MGI Ref ID J:92540)
  • zygous females and homozygous mutant males (7.1 ¿ 0.40)
  (MGI Ref ID J:92540)

• decreased litter size
  • litters born to homozygous mutant females are significantly smaller than those born to heterozygous females regardless of the male genotype
  (MGI Ref ID J:92540)

taste/olfaction phenotype

• impaired olfaction
  • mice exhibit deficits in detecting or discriminating chemically-related odors
  (MGI Ref ID J:166638)

cellular phenotype

• asthenozoospermia
  • many nonmotile sperm exhibit a quivering head and midpiece but no forward movement, confirming that cells are alive
  (MGI Ref ID J:115434)
  • Normal - however, no significant differences in sperm viability, senescence rate or spontaneous acrosome reaction rate are observed between mutant and wild-type sperm before and after capacitation
  (MGI Ref ID J:115434)
  • mutant sperm initially appear to swim normally but fail to maintain progressive forward motility
  (MGI Ref ID J:115434)
  • only few mutant sperm retain rapid swimming velocities and display hyperactivated swimming patterns following in vitro capacitation
  (MGI Ref ID J:115434)

mammalian phenotype

• reproductive system phenotype
  • Normal - female homozygotes have normal ovaries and enter puberty at the expected age, with no significant differences in the onset of vaginal opening or cornification relative to wild-type or heterozygous control females
  (MGI Ref ID J:92540)
  • Normal - testicular weight, total sperm number, and sperm morphology appear normal
  (MGI Ref ID J:115434)
  • Normal - male homozygotes are fertile and exhibit an apparently normal mating behavior
  (MGI Ref ID J:92540)

taste/olfaction phenotype

• impaired olfaction
  • mice exhibit deficits in detecting or discriminating chemically-related odors
  (MGI Ref ID J:166638)